Original Article

Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human oral squamous cell carcinoma cells via suppressing survivin expression

Meng-dong Liu, Shi-jiang Xiong, Fei Tan, Yi Liu
DOI: 10.1038/aps.2015.152


Aim: A previous study has shown that physcion 8-O-β-glucopyranoside (PG) derived from Rumex japonicas Houtt causes apoptosis and blocks cell cycle progression in human lung cancer cells. In the present study we investigated the molecular mechanisms underlying PG-induced cancer cell apoptosis.
Methods: Human OSCC-derived cell line KB was treated PG (10, 20, 50 μg/mL). Cell apoptosis was detected with flow cytometry. Mitochondrial membrane potential (MMP) and release of cytochome C from mitochondria were measured; the expression of relevant signaling proteins was analyzed using Western blotting or qRT-PCR. For evaluation of in vivo anticancer action, nude mice grafted with KB cells were treated with PG (10, 20, 40 mg·kg−1·d−1, ip) for 24 days.
Results: PG dose-dependently suppressed cell proliferation and induced apoptosis in KB cells. PG-induced apoptosis was mediated via the intrinsic mitochondrial pathway, as evidenced by the decreased Bcl-2, increased Bax and Bax/Bcl-2 ratio, as well as the loss of MMP, caspase-9 activation, and increased cytosolic cytochrome c. Furthermore, PG suppressed the expression of survivin, whereas overexpression of survivin markedly attenuated PG-induced apoptosis. Meanwhile PG increased the expression of tumor suppressor PTEN, and decreased p-Akt, p-GSK3β and miR-21 levels. Pharmacological activation of Akt/GSK3β signaling or transfection with miR-21 mimic abolished PG-induced survivin reduction and cell apoptosis. Similar results were observed in PG-treated nude mice grafted with KB cells.
Conclusion: Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human OSCC cells by suppressing survivin expression via miR-21/PTEN/Akt/GSK3β signaling pathway.
Keywords: physcion 8-O-β-glucopyranoside; human oral squamous cell carcinoma; mitochondria-dependent apoptosis; survivin; miR-21; PTEN; Akt/GSK3β

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